ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.865_866del (p.Lys289fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004018375 SCV004848167 likely pathogenic Ornithine carbamoyltransferase deficiency 2018-06-09 criteria provided, single submitter clinical testing The p.Lys289fs variant in OTC has not been previously reported in individuals with ornithine transcarbamylase (OTC) deficiency and or in large population studies. This variant is located in the last three bases of the exon, which is part of the 5’ splice region. Computational tools do predict altered splicing. Furthermore, this variant may cause a frameshift, which alters the protein’s amino acid sequence beginning at position 289 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the OTC gene is an established disease mechanism in OTC deficiency. In summary, although additional studies are required to fully establish its clinical significance, the p.Lys289fs variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1; PM2.

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